Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...
Reexamination Certificate
2000-12-21
2002-07-02
McKane, Joseph K. (Department: 1626)
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Having -c-, wherein x is chalcogen, bonded directly to...
C548S247000
Reexamination Certificate
active
06414004
ABSTRACT:
This is a 371 of international application PCT/EP99/03153 with international filing date of May 7, 1991 published in English.
The invention relates to compounds with a 3-substituted 5-aryl-4-isoxazolecarbonitrile structure, of formula (I)
wherein
R is hydrogen, halogen, COOH, COOR″, C
1
-C
4
alkyl, NO
2
, OR″, phenyl;
R′ is C
1
-C
4
alkyl, COOH, COOR″;
R″ is C
1
-C
4
alkyl;
X is an oxygen or sulfur atom or a single bond;
n is an integer 1-6,
with the proviso that, when R′ is CH
3
, R is different from hydrogen;
said compounds having antiviral activity.
In Acts of the First Italian-Swiss Meeting of Medicinal Chemistry (Turin, 1997) derivatives of formula (I) with R=H and R′=CH
3
supposedly having antiviral activity, are cited. It has now been found that both said derivatives and those of formula (I) with R different from hydrogen, have indeed antiviral activity which is of great interest as far as a series of viruses, are concerned.
The invention also relates to pharmaceutical compositions containing as active ingredient at least one compound of formula (I) wherein R′, R″, X and n have the meanings defined above, whereas R is hydrogen, also when R′=CH
3
, optionally combined with one or more other active principles.
Preferred compounds of formula (I) in the compositions according to the invention are those wherein R is hydrogen, bromine, COOH, COOCH
3
, CH
3
, NO
2
; R′ is CH
3
; X is an oxygen atom; n is 2, 3 or 4. Particularly preferred are those compounds wherein R is at the 4-position on the phenyl ring.
According to the invention, compounds (I) are obtained by reacting an intermediate of formula (II) with a 5-(4-hydroxyphenyl)-4-isoxazolecarbonitrile having a R′S substituent at the 3-position, for example with 3-methylthio-5-(4-hydroxyphenyl)-4-isoxazolecarbonitrile (III), according to scheme A shown hereinbelow:
wherein R, X and n have the meanings defined above, whereas Z is a halogen atom, preferably a bromine atom.
Intermediate (III) is obtained following scheme B; intermediates of formula (III) wherein the methyl group is substituted by carboxyl or carbalkoxyl can be prepared analogously,
whereas intermediates (II) can be prepared according to per se known methods.
The reaction yielding final compounds (I), according to scheme A, is suitably carried out in the presence of an acid-binding agent, for example potassium carbonate, in inert solvents, at temperatures ranging from room temperature to about 100° C. Suitable solvents are, for example, ketones such as acetone, methyl ethyl ketone, methyl isopropyl ketone, or ethers such as tetrahydrofuran or dioxane.
REFERENCES:
Campagne et al. Isoxazoles with Antiviral Activity. First Italiam Swiss Meeting on Medicinal Chemistry, (Turin, 1997), 206.
Campagna Rossella Maria
Castro Angelo
Garozzo Adriana
Geremia Ernesto
Guerrera Francesco
Anderson Rebecca
McKane Joseph K.
Schneider Walter H.
Universita' Degli Studi di Catania
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